The proposed project represents an investigation of the structure of nerve fiber membranes using the techniques of electron microscopy and freeze-fracturing. The specialized regions of these membranes that will be studied include the node of Ranvier, which is an electrically excitable membrane containing high concentrations of ionophores, and the paranodal regions on either side, where complex junctions form between the axolemma and the terminal edges of the myelin sheath, as well as the internodal portions of the axolemma. Changes in intramembranous particles and in other membrane constituents under a variety of different physiological and pathological conditions will be followed in order to assess the functional roles and detailed structure of the various components. Comparative studies will be undertaken as a way of determining which structural features of these membranes are phylogenetically stable, and regenerating axons will be examined to assess the sequence in the development of membrane specializations.